AccuO 2 Oximetry-Driven Oxygen-Conserving Device Versus Fixed-Dose Oxygen Devices in Stable COPD Patients

AccuO 2 Oximetry-Driven Oxygen-Conserving Device Versus Fixed-Dose Oxygen Devices in Stable COPD Patients Kathryn L Rice MD, Matthew F Schmidt PhD, John S Buan PhD, Francene Lebahn CCRC MT, and Ted K Schwarzock BACKGROUND: Because standard home oxygen (O 2 ) systems deliver O 2 at fixed rates, these systems are not designed to ensure optimal oxygen delivery based on physiologic need. We tested the ability of the AccuO 2 (OptiSat Medical, Minneapolis, Minnesota), a portable, closed-loop, oximetrydriven, O 2 -conserving device to maintain S po2 at > 90%, compared to continuous-flow oxygen and a standard O 2 -conserving device (CR-50, Puritan-Bennett, Pleasanton, California). METHODS: We randomly assigned 28 patients who were on continuous home O 2 for COPD to use each of 3 O 2 delivery systems (continuous-flow O 2, CR-50, and AccuO 2 ) for 8 hours a day, for 2 consecutive days, at home, at their current O 2 prescription. We recorded S po2 and calculated the conservation ratio (duration of a given O 2 supply with an O 2 -conserving device compared to continuous-flow O 2 ). RESULTS: Twenty-two patients completed all 3 study arms; 2 additional patients completed the AccuO 2 arm and the continuous-flow O 2 arm. The mean SD S po2 was 92 4% with continuousflow O 2,92 4% with the CR-50, and 91 2% with AccuO 2 (P.006 for the AccuO 2 vs continuous-flow O 2, P.03 for the AccuO 2 vs the CR-50). S po2 variability was less with the AccuO 2 (P <.001 vs continuous-flow O 2 and vs the CR-50). The conservation ratios were 9.9 7.3 for the AccuO 2 and 2.6 1.0 for the CR-50 (P <.001). CONCLUSIONS: Compared to continuous-flow O 2 or the CR-50, the AccuO 2 maintained S po2 closer to the target, and AccuO 2 had a higher conservation ratio than CR-50. Key words: COPD; long-term oxygen therapy; oxygenconserving device; pulse oximetry. [Respir Care 2011;56(12):1901 1905] Introduction Chronic obstructive pulmonary disease (COPD) is estimated to afflict 24 million people in the United States and is the fourth leading cause of death. 1 In 2006 in the United States there were over 124,000 deaths attributable to COPD and allied conditions, 670,000 hospitalizations, and 16.3 million physician office visits. 1 The total economic cost of COPD for 2010 in the United States is projected to be $49.9 billion, 1 Dr Rice is affiliated with the Pulmonary Section, Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota. Dr Schmidt, Dr Buan, and Mr Schwarzock are affiliated with OptiSat Medical, Minneapolis, Minnesota. Ms Lebahn is affiliated with the Academic Health Center, University of Minnesota, Minneapolis, Minnesota. This research was partly supported by the University of Minnesota Technology Partnership Fund and the Minneapolis Veterans Affairs Research Service. Dr Rice has disclosed a relationship with Wyeth Pharmaceuticals. Dr Schmidt, Dr Buan, and Mr Schwarzock have disclosed relationships with OptiSat Medical. Ms Lebahn has disclosed no conflicts of interest. and long-term oxygen therapy (LTOT) accounts for a substantial portion of that cost. Medicare expenditures for LTOT exceed $2 billion annually. 2 Portable oxygen (O 2 ) accounts for a substantial portion of the provider cost of LTOT. 3 SEE THE RELATED EDITORIAL ON PAGE 1975 Most LTOT systems provide a continuous fixed flow of O 2. The prescribed O 2 flow is typically based on a single measurement and aimed at keeping S po2 90%. 4 O 2 - conserving devices are added to portable LTOT systems for patient convenience and to reduce O 2 waste. The available continuous-flow and O 2 -conserving systems are not designed to monitor and maintain S po2 90% on a minute-to-minute basis. We tested a prototype oximetry-driven O 2 -conserving device, the AccuO 2 (OptiSat Medical, Minneapolis, Minnesota) (Fig. 1), against standard continuousflow O 2 and a standard O 2 -conserving device (CR-50, Puritan-Bennett, Pleasanton, California). RESPIRATORY CARE DECEMBER 2011 VOL 56 NO 12 1901

Oxygen Delivery Systems Fig. 1. The AccuO 2 closed-loop oximetry-driven portable O 2 -conserving device. Methods This study was approved by the Minneapolis Veterans Affairs Medical Center Human Studies Committee. Written, informed consent was obtained from all subjects. The study was performed at the Minneapolis Veterans Affairs Medical Center between 1999 and 2000 and was therefore not subject to the requirement for clinic trial registration. Dr Rice had full access to all the study data and takes full responsibility for the integrity and accuracy of the data analysis. Subjects Via telephone, we recruited patients receiving LTOT for COPD from the Minneapolis Veterans Affairs Medical Center home O 2 roster. According to the policy of the medical center, all the patients were originally prescribed LTOT to achieve a target S po2 of 90 92%. The main inclusion criterion was a current LTOT prescription at a flow of 1 3 L/min for 18 24 hours per day. Exclusion criteria were current tobacco smoking, hospitalization for any reason within the last month, any respiratory drug prescription change in the previous 2 weeks, non-ambulatory status, active alcohol or drug addiction, any unstable disease state, and LTOT prescribed for conditions other than COPD. Dr Rice presented a version of this paper at the 103rd International Conference of the American Thoracic Society, held May 18 23, 2007, in San Francisco, California. Correspondence: Kathryn L Rice MD, Pulmonary Section, Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Minneapolis MN 55417. E-mail: kathryn.rice@va.gov. DOI: 10.4187/respcare.01059 With the continuous-flow system or the CR-50, O 2 was delivered via nasal cannula at the flow previously prescribed for that patient to maintain S po2 90%. The AccuO 2 (see Fig. 1) is designed to maintain S po2 at a selected target at all times. The outputs of the pulse oximeter and inhalation sensor are continuously monitored by the microcontroller. The volume of O 2 to be delivered is calculated by a modified proportional integral differential control algorithm, based on the difference between the observed and desired S po2 values and the trend in that difference. Oximeter data and O 2 pulse/bolus size are measured and updated every second. Starting from a steady-state situation (ie, the patient s S po2 is stable at the target), the AccuO 2 begins increasing the O 2 dose on the first inhalation after a valid S po2 reading below the target (ie, within 1 2 s). Signal averaging built into the oximeter gives an overall time constant of about 5 10 seconds. The oximeter s output includes error flags for a detached sensor, low-perfusion state, and heart rates of 40 beats/min and 180 beats/min. If an error condition occurs, the AccuO 2 continues to deliver O 2 during every inhalation at the same level administered prior to the error condition for 15 seconds. If the error condition persists for 15 seconds the AccuO 2 defaults to a standard fixed-bolus, prescription-equivalent, pulse-delivery mode (33 ml/breath bolus). The maximum O 2 bolus was set at 66 ml/breath (equivalent to 4 L/min continuous flow). All the O 2 used in this study was in E-size cylinders. In-Clinic Testing In baseline testing with each patient we confirmed the ability of the continuous-flow O 2 system and the CR-50 to achieve S po2 90%, and the ability of each patient to trigger the CR-50. We tested several prototypes of the AccuO 2 in the clinic to determine the appropriate proportional integral differential control parameters and to verify and refine the respiration-sensing algorithm. To determine O 2 savings and verify that the prototype AccuO 2 maintained the target S po2, we tested the phase-1 prototype and proportional integral differential control parameters under supervision in the clinic, with patients at rest and while walking at their own pace for 15-min periods, if possible, to mimic home activities. The final version of the AccuO 2, built by a contract manufacturer, was tested in the clinic with a finger oximetry sensor (8000AA-3, Nonin Medical, Plymouth, Minnesota) for up to 6 hours, during which time the patients were encouraged to mimic their usual activity levels by walking at their own pace within the Minneapolis Veterans Affairs Medical Center. After reviewing the preliminary results, our institutional review board gave further approval for the in-home testing protocol. 1902 RESPIRATORY CARE DECEMBER 2011 VOL 56 NO 12

In-Home Testing Patients were studied on their standing O 2 prescriptions, all of which were 3 L/min. We asked the patients to use each O 2 system, in random order, at home, for 8 hours a day, during daytime hours only, on 2 consecutive days. We encouraged the patients to go about their normal daily activities during every study period. The target S po2 for the AccuO 2 was set at 90%. In all 3 treatment arms the patients wore a logging pulse oximeter (8500M, Nonin Medical, Plymouth, Minnesota). The average duration of home use for each O 2 delivery device was based on the amount of time recorded by the oximeter. We continuously recorded the patients activity levels with an actigraph (Actiwatch, Philips Respironics, Murrysville, Pennsylvania) during daytime hours only. Readings above zero during any 15-second period were counted as activity. To determine the amount of O 2 used during each 2-day period, we weighed the specially marked O 2 cylinders before and after each 2-day period. A full E-cylinder nominally contains 680 L of O 2. The molecular weight of O 2 is 31.9988 g/mole, and molar volume is 24.465 L/mole at 25 C, so 680 L of O 2 weighs 889.4 g. We calculated the conservation ratio as the duration a given amount of O 2 lasted with an O 2 -conserving device, compared to during continuous-flow O 2 therapy. Fig. 2. Flow chart. Statistical Analysis We analyzed the S po2 values and conservation ratios with the Mann-Whitney test. Differences in standard deviations were analyzed with the 2-tailed Kolmogorov- Smirnov test. We report mean SD values. Results Twenty-eight patients (all male, mean age 72.3 y, age range 60 81 y) consented to participate in the in-home study (Fig. 2), but 3 of the 28 withdrew consent before testing any device. Twenty-two patients completed all 3 study arms; 2 additional patients used only the AccuO 2 and the continuous-flow system. One patient used only the CR-50 and continuous O 2. The mean S po2 during the in-home study periods was significantly lower with the AccuO 2 (91 2%) than with the CR-50 (92 4%, P.03) or continuous-flow O 2 (92 4, P.006) (Fig. 3). AccuO 2 appeared to reduce the amount of time spent at low S po2, although this difference was not statistically significant (Fig. 4). The S po2 was 88% for more than 50% of the study period in 0, 2, and 4 patients, respectively, with the AccuO 2, CR-50, and continuous-flow O 2. The amount of time spent with S po2 90% was significantly less with the AccuO 2 (see Fig. 4). S po2 was 95% more than 50% of the time in 0, 9, and Fig. 3. Individual and mean S po2 values during 48-hour periods at home. P.006 for AccuO 2 versus continuous-flow O 2, P.03 for AccuO 2 versus CR-50. 6 patients, respectively, with the AccuO 2, CR-50, and continuous-flow O 2.S po2 variability was significantly lower with the AccuO 2. The S po2 standard deviation was significantly smaller with the AccuO 2 : the means of the individual patients for the AccuO 2, CR-50, and continuousflow O 2 were 2.4%, 3.2%, and 3.5%, respectively (P.001 for AccuO 2 versus CR-50 or continuous-flow O 2 ). The average percentage of invalid/error oximeter data across all arms and patients was 3.3 2.7%, and there were no statistically significant differences between the arms. The AccuO 2 applies more stringent requirements on the oximeter data to be in closed-loop mode: the average percentage of time in the fixed-dose default mode (ie, not in closed-loop) was 14.4 12.1%. Twenty-one of 24 patients were in closedloop mode more than 75% of the time with the AccuO 2. RESPIRATORY CARE DECEMBER 2011 VOL 56 NO 12 1903

Fig. 4. Cumulative percent of time under various S po2 levels during two 8-hour periods on 2 consecutive days at home. P values compared to continuous-flow O 2 for each 1% increment increase in S po2 are represented by open circles for P values.05, and by Xs for P values.05. The average duration of home use was 15.5 2.0 hours with the AccuO 2, 14.3 2.5 hours with the CR-50, and 15.8 1.3 hours with the continuous-flow O 2 system. Less supplemental O 2 was required to maintain the target S po2 with the AccuO 2. With continuous-flow O 2 as the reference, the mean conservation ratios for the AccuO 2 and CR-50 were 9.9 7.3 and 2.6 1.0, respectively (P.001) (Fig. 5). The patients daytime home activity levels were not significantly different with the different O 2 systems. The average actigraphy output counts were: AccuO 2 20.5 59.8, CR-50 22.0 65.3, and continuous-flow O 2 26.3 77.5. The mean percentages of time spent in activity during the 8-hour study periods were: AccuO 2 31.6%, CR-50 32.0%, and continuous-flow O 2 32.0%. We asked the patients to rank the O 2 systems according to their preference (1 most preferred, 3 least preferred), and the mean scores were: AccuO 2 2.1 0.9, CR-50 1.7 0.7, and continuous-flow O 2 2.2 0.8. Discussion The AccuO 2 maintained a clinically acceptable S po2 with less S po2 variation and lower O 2 consumption than CR-50 or continuous-flow oxygen. Mean S po2 was lowest with AccuO 2, because the AccuO 2 is designed to maintain the S po2 as close as possible to 90%, consistent with the therapeutic goal of the Nocturnal Oxygen Therapy Trial, 5 in which patients with a baseline P O2 55 mm Hg were given supplemental O 2 to achieve a P O2 range of 60 mm Hg (which approximately corresponds to an S po2 of 90%) to 80 mm Hg. Based on the results of that trial, there is general consensus that the S po2 goal of LTOT should be 90%. The current COPD treatment guidelines 4 recommend titrating LTOT to S po2 90%. Available evidence does not support a higher Fig. 5. Mean conservation ratios during 48-hour periods at home. *P.001 for AccuO 2 versus CR-50 and for AccuO 2 versus continuous-flow O 2. target S po2, as shown in a study by Gorecka and colleagues, in which a target P O2 of 65 mm Hg in patients with less severe hypoxemia did not confer a survival benefit. 6 Patients treated with continuous LTOT have been reported to spend 10 30% of their time in a hypoxic state, including both sleep and waking hours. 7-10 The primary advantage of oximetry-driven O 2 delivery is maintaining the S po2 at or near 90% while reducing O 2 waste. The mean conservation ratio with the AccuO 2 was more than 3 times that with the CR-50 and 9 times that with continuous-flow O 2. Although we used E cylinders in this study, by extending the duration with any cylinder size, the AccuO 2 would provide a similar duration benefit for patients using smaller, less cumbersome tanks, and might substantially reduce the cost of LTOT with all cylinder sizes, because portable equipment accounts for a substantial portion of LTOT costs. Although we observed a non-significant reduction in desaturations, this observation should be considered hypothesis-generating only: further studies with sufficient power to determine this effect are needed. Because we chose a single target S po2 of 90% for the AccuO 2, we did not determine its effectiveness or O 2 savings at other target S po2 levels. The difference in O 2 savings between the AccuO 2 and standard O 2 delivery devices might be smaller if standard O 2 -conserving devices were more tightly set to achieve S po2 of 90%, although the practicality of that approach is questionable. We believe testing patients on their standing LTOT prescriptions is applicable to clinical practice, as all patients were originally prescribed LTOT to achieve a target S po2 of 90 92%. Limitations Because the in-home study period was limited to 2 consecutive days, the performance of the AccuO 2 over longer 1904 RESPIRATORY CARE DECEMBER 2011 VOL 56 NO 12

periods and under more varied clinical circumstances is not known. The actigraphy data did not allow us to distinguish between sleep and inactivity, because readings above zero were counted as activity. We doubt that a reading of zero indicated that the patient was asleep, however, because the actigraph readings were zero more than 60% of the time during the day. The patients activity levels were similar across all 3 arms, so the activity differences could not account for the substantial O 2 savings we observed with the AccuO 2. Although the patient survey results suggest that the AccuO 2 was as well tolerated as the CR-50, more detailed information on specific aspects of patient preference, such as comfort or convenience, is needed to better determine the feasibility of the AccuO 2. Options for potentially less burdensome oximeter sensors, such as a reflectance sensor on the forehead or behind the ear, an ear-lobe sensor, or wireless oximeters, should be considered for future testing. Closed-loop, oximetry-driven O 2 delivery has potential application beyond ambulatory LTOT. Almost 50% of patients on LTOT for COPD are reported to experience substantial nocturnal desaturation with standard O 2 delivery systems. 10 Although we did not study our patients during sleep, the AccuO 2 has potential application for maintaining a therapeutic nocturnal S po2. Oximetry-driven O 2 delivery systems may also have applications in settings other than the treatment of patients with stable COPD. In patients who are hospitalized for COPD exacerbation, pulse oximetry-driven O 2 delivery could be used to avoid the high S po2 values that have been associated with acute CO 2 retention. Systems driven by continuous oximetry and blood-gas data have been used to automate O 2 delivery in neonates and pre-term infants. 11-13 Conclusions This study provides preliminary evidence that O 2 delivery with the AccuO 2 is as or more effective than standard O 2 delivery systems in maintaining a target S po2 via continuous adjustment of O 2 delivery based on physiologic need. By improving O 2 conservation, AccuO 2 may improve patient convenience, potentially at a lower cost. Further studies should be done to confirm the observation that patients appear to spend less time at low S po2 with AccuO 2. Long-term studies, particularly in the ambulatory setting in patients with various levels of disease stability and other clinical conditions, are also needed to determine the impact of this novel O 2 delivery system. REFERENCES 1. National Institutes of Health, National Heart, Lung, and Blood Institute. 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Incidence of nocturnal desaturation while breathing oxygen in COPD patients undergoing long-term oxygen therapy. Chest 2000; 117(3):679-683. 11. Beddis IR, Collins P, Levy NM, Godfrey S, Silverman M. New technique for servo-control of arterial oxygen tension in preterm infants. Arch Dis Child 1979;54(4):278-280. 12. Morozoff PE, Evans RW. Closed-loop control of SaO 2 in the neonate. Biomed Instr Tech 1992;26(2):117-123. 13. Sano A, Kikucki M. Adaptive control of arterial oxygen pressure of newborn infants under incubator oxygen treatments. IEE Proc Pt 1985;132(5):205-211. This article is approved for Continuing Respiratory Care Education credit. For information and to obtain your CRCE (free to AARC members) visit www.rcjournal.com RESPIRATORY CARE DECEMBER 2011 VOL 56 NO 12 1905